Clinical Trial Results:
A combined Phase IIa / IIb study of the efficacy, safety, and tolerability of repeated topical doses of regorafenib eye drops, in treatment-naive subjects with neovascular age related macular degeneration
Summary
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EudraCT number |
2012-003763-22 |
Trial protocol |
HU DE CZ SK |
Global end of trial date |
17 Jun 2015
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Results information
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Results version number |
v1 |
This version publication date |
28 Jun 2016
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First version publication date |
28 Jun 2016
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY73-4506/15984
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02222207 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bayer HealthCare AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer HealthCare AG, clinical-trials-contact@bayerhealthcare.com
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Scientific contact |
Therapeutic Area Head, Bayer HealthCare AG, clinical-trials-contact@bayerhealthcare.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Jun 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Jun 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objectve for part A is to assess the effect of treatment with regorafenib eye drops on visual acuity at Study Week 4 and at Study Week 12 in subjects with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Oct 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Czech Republic: 13
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Country: Number of subjects enrolled |
Spain: 14
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Hungary: 10
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Country: Number of subjects enrolled |
Israel: 8
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Worldwide total number of subjects |
52
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EEA total number of subjects |
44
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
38
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85 years and over |
7
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Recruitment
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Recruitment details |
The study was conducted at 27 centers, between 10 October 2014 (first subject first visit) and 17 June 2015 (last subject last visit). | ||||||||||||||||
Pre-assignment
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Screening details |
Study was planned to be conducted in 2 parts, Part A and B, in Part A 89 subjects were enrolled, of them 37 were screen failure and 52 were assigned to treatment, 1 subject was excluded from all analysis sets due to protocol deviations and 51 subjects were analyzed. Part B was not initiated and the study terminated following completion of Part A. | ||||||||||||||||
Period 1
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Period 1 title |
Overall Trial
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Is this the baseline period? |
No | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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Part A Regorafenib | ||||||||||||||||
Arm description |
Subjects self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL), 1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Regorafenib
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Investigational medicinal product code |
BAY73-4506
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Other name |
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Pharmaceutical forms |
Eye drops
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Routes of administration |
Ocular use
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Dosage and administration details |
Self-administration of 30 mg/mL, 25 mcL, 1 drop of Regorafenib eye drops, TID to the study eye for 12 weeks.
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Period 2
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Period 2 title |
Baseline period
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Is this the baseline period? |
Yes [1] | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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Part A Regorafenib | ||||||||||||||||
Arm description |
Subjects self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Regorafenib
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Investigational medicinal product code |
BAY73-4506
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Other name |
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Pharmaceutical forms |
Eye drops
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Routes of administration |
Ocular use
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Dosage and administration details |
Self-administration of 30 mg/mL, 25 mcL, 1 drop of Regorafenib eye drops, topically TID to the study eye for 12 weeks.
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Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Baseline data is available only for treated participants and not randomized participants, hence this period has been created to report the baseline data. |
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Baseline characteristics reporting groups [1]
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Reporting group title |
Part A Regorafenib
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Reporting group description |
Subjects self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks. | |||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: Not all the enrolled subjects were treated with study drugs. As baseline only included treated subjects, the worldwide number enrolled in the trial differs with the number of subjects reported in the baseline period. |
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End points reporting groups
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Reporting group title |
Part A Regorafenib
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Reporting group description |
Subjects self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL), 1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks. | ||
Reporting group title |
Part A Regorafenib
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Reporting group description |
Subjects self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks. | ||
Subject analysis set title |
Full Analysis Set (FAS-Part A)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
FAS (N=51) included subjects who received at least one dose of study medication.
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Subject analysis set title |
Safety analysis set (SAF-Part A)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
SAF (N=51) included subjects who received at least one dose of study medication.
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End point title |
Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Study Week 4 for Study Part A [1] | ||||||||
End point description |
Subjects will be assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS. The subject’s ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For patients that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.
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End point type |
Primary
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End point timeframe |
Baseline, Week 4
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis were provided as an attachment |
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Attachments |
Untitled (Filename: 15984_Statistical analysis of change in BCVA in ETDRS letter score from baseline at Study Week 4.pdf) |
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Notes [2] - FAS |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in BCVA as Measured by ETDRS Letter Score at Study Week 12 for Study Part A [3] | ||||||||
End point description |
Subjects were assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS protocol. ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For patients that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis were provided as an attachment |
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Attachments |
Untitled (Filename: 15984_Statistical analysis of change in BCVA in ETDRS letter score at Study Week 12.pdf) |
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Notes [4] - FAS |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Individual Changes in BCVA of greater than equal to (>=) 0 Letters of Vision From Study Week 4 to Week 12 for Study Part A | ||||||||
End point description |
Subjects were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For patients that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.
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End point type |
Secondary
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End point timeframe |
Week 4, Week 12
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Notes [5] - FAS |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With a Loss in BCVA of >= 10 Letters From Baseline to Study Week 12 for Study Part A | ||||||||
End point description |
Subjects were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For patients that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Notes [6] - FAS |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From the start of study treatment until 30 days after last dose of study drug treatment (up to Week 16)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Part A Regorafenib
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Reporting group description |
Subjects self-administered 30 mg/mL, 25 mcL, 1 drop of regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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18 Feb 2015 |
Addition of subfoveal fibrosis in exclusion criteria; Clarification of the exclusion of subjects requiring steroid treatment; Deletion of controlled glaucoma as an exclusion criteria; Inclusion of a description of how ranibizumab will be used. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
As the study was prematurely terminated since pre-defined proof of concept (PoC) criteria were not met in Part A, hence part B was not initiated. Part B related end points and data were not reported since it is not conducted. |